Effects of hypothyroidism on the detyrosylation of alpha-tubulin in the parallel fibers of the developing rat cerebellar cortex.

The immunocytochemical staining of tyrosylated alpha-tubulin using the specific monoclonal antibody YL 1/2 decreases dramatically in the parallel fibers of the rat cerebellum during development. Detyrosylation starts at 14 days in the deeper part of the molecular layer and then spreads over the entire molecular layer within a week. Thyroid deficiency induces a marked delay in alpha-tubulin detyrosylation in the parallel fibers. Detyrosylation begins only at the age of 28 days in hypothyroid animals. Immunobinding assays of detyrosylated and tyrosylated alpha-tubulin concentrations in the cerebellar supernatant of developing rats confirm that thyroid deficiency increases the tyrosylated alpha-tubulin content at 21 and 35 days. Short-term thyroxine treatment (daily from day 8, 10 or 12, to day 14) do not induce the normal pattern of tubulin detyrosylation starting at 14 days, although they do induce parallel fiber lengthening. Daily treatment from birth is required to produce the alpha-tubulin modification found in normal rats. We propose that the microtubule detyrosylation which occurs during axonal maturation is not a prerequisite for axon growth and synaptic differentiation, but may rather be implicated in the stabilization of microtubules in the mature axons.